Bone Abstracts

Tenofovir disoproxil fumarate (TDF) is a critical component of first-line antiretroviral regimens for HIV worldwide. However, TDF-containing regimens have been associated with decreased bone mineral density and increased fracture risk, which may in part be mediated through secondary elevations in parathyroid hormone (PTH). Prior cross-sectional data suggest vitamin D binding protein (DBP) levels may increase with TDF exposure leading to a functional vitamin D deficiency, which...

Objectives: XLH features renal phosphate (Pi) wasting, hypophosphatemia, rickets, and skeletal deformities from elevated circulating levels of fibroblast growth factor 23 (FGF23). KRN23, an investigational fully human monoclonal antibody, binds FGF23 and inhibits its action. Our Phase 2 study of KRN23 in XLH children (ages 5–12 years) is demonstrating improvements in serum Pi and rickets. Here we present our Phase 2 trial evaluating the efficacy and safety of KRN23 in you...

Introduction: Lower bone mineral content (BMC) has been reported in HIV-infected children, as well as those on ritonavir-boosted lopinavir (LPV/r)-based antiretroviral therapy (ART). Older studies of children with HIV report increased bone resorption, but data with current antiretroviral regimens are limited.Methods: This analysis presents data from the CHANGES Bone Study (Johannesburg, South Africa). Whole body (WB) BMC was assessed by dual-energy X-ray...

Objectives: Children with Perthes disease may present with altered walking patterns even at the healed stage of the disease. The aim of the study was to assess the walking endurance, fatiguability and gait changes of children with healed Perthes disease, and to determine if walking endurance is associated with hip function and quality of life.Methods: Fifty-one children (38 males) aged 8–16 years with >3 years post-diagnosis of Perthes disease c...

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We recently established a large animal model of osteoporosis in sheep using hypothalamic–pituitary disconnection (HPD). As central regulation is important for bone metabolism, HPD-sheep developed severe osteoporosis because of low bone turnover. In this study we investigated metaphyseal fracture healing in HPD-sheep. To elucidate potential pathomechanisms, we included a treatment group receiving thyroxine (T4) and 17β-estradiol. Because clinically osteopor...

Introduction: The prospective, single-arm, open-label ZOTECT study was designed to assess the effect of zoledronic acid (ZOL) on bone-marker levels and potential correlations with disease outcomes in bisphosphonate-naive patients with bone metastases.Methods: Patients with bone metastases from prostate cancer (PC; n=301) or breast cancer (BC; n=99) who have not received bisphosphonates for ≥6 months were enrolled at 98 sites in Ge...

Autosomal dominant osteopetrosis type II (ADO2) is a rare osteosclerotic disease due heterozygous missense mutations of the CLC7 gene encoding the type seven chloride channel. Our two labs independently generated the first C57 black 6 (B6) mouse model of ADO2 by inserting the pG213R-clc7 mutation. Homozygous mice showed lack of tooth eruption and died within 30 days of age with severe osteopetrosis and central nervous system degenera...

Autosomal dominant type II osteopetrosis (ADO2) is a rare osteosclerotic disorder due to heterozygous missense mutations of CLC7 gene encoding the type 7 chloride channel. Our two labs (L’Aquila and Indianapolis) independently generated the first C57 black 6 (B6) mouse model of ADO2 by inserting the pG213R-clc7 mutation. We created pG213R-clc7 KI mice using a gene targeting approach. Homozygous mice showed lack of tooth eruption and died within ...

Fibrous dysplasia (FD) is a benign skeletal disease caused by activating mutations of Gsα. These mutations lead to formation of abnormal and mechanically unsound bone and fibrotic tissue. Clinical sequelae include deformity, fracture, and pain. Studies in bisphosphonates have shown improvement in bone pain and inconsistent effects on FD mineralization; however interpretation has been limited by a lack of controlled trials.Objecti...